Division of Endocrinology, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048, USA.
Mol Cell Endocrinol. 2012 Oct 15;362(1-2):104-9. doi: 10.1016/j.mce.2012.05.020. Epub 2012 Jun 15.
We tested effects of selective somatostatin receptor 2 (SST2) agonist BIM-23120, SST5 agonist BIM-23206 and chimeric somatostatin-dopamine molecules (SRIF/DA) BIM-23A760 and BIM-23A761 on GH and PRL secretion and gene expression in human GH/PRL-secreting pituitary tumors in vitro. In "responders" group BIM-23120 suppressed GH levels by 26±4%, BIM-23206 by 31±5%, BIM-23A760 by 23±4%, BIM-23A761 by 39±8% and D(2)-dopamine agonist BIM-53097 by 31±5%. Using real-time PCR we demonstrated that GH inhibition was not accompanied by decreased GH mRNA levels. PRL secretion was inhibited by BIM-23A760 (29±5%), BIM-23A761 (34±4%), BIM-23206 (26±4%) and BIM-53097 (36±2%). SRIF/DA and BIM-53097 also suppressed PRL mRNA levels. Concluding, SST2 and SST5 agonists and SRIF/DA inhibit GH secretion, but do not suppress GH gene transcription. SRIF/DA and BIM-53097 inhibit both PRL secretion and PRL gene expression. SST5 agonist inhibits PRL secretion, but does not suppress PRL gene expression. D(2) affinity is crucial in SRIF/DA action on PRL gene expression.
我们测试了选择性生长抑素受体 2（SST2）激动剂 BIM-23120、SST5 激动剂 BIM-23206 和嵌合生长抑素-多巴胺分子（SRIF/DA）BIM-23A760 和 BIM-23A761 对体外人 GH/PRL 分泌性垂体肿瘤中 GH 和 PRL 分泌和基因表达的影响。在“应答者”组中，BIM-23120 使 GH 水平降低 26±4%，BIM-23206 降低 31±5%，BIM-23A760 降低 23±4%，BIM-23A761 降低 39±8%，D2-多巴胺激动剂 BIM-53097 降低 31±5%。使用实时 PCR，我们证明 GH 抑制并不伴有 GH mRNA 水平降低。BIM-23A760（29±5%）、BIM-23A761（34±4%）、BIM-23206（26±4%）和 BIM-53097（36±2%）抑制 PRL 分泌。SRIF/DA 和 BIM-53097 也抑制 PRL mRNA 水平。总之，SST2 和 SST5 激动剂和 SRIF/DA 抑制 GH 分泌，但不抑制 GH 基因转录。SRIF/DA 和 BIM-53097 抑制 PRL 分泌和 PRL 基因表达。SST5 激动剂抑制 PRL 分泌，但不抑制 PRL 基因表达。D2 亲和力在 SRIF/DA 对 PRL 基因表达的作用中至关重要。
